Mosquito-borne diseases are major causes of mortality world-wide, with malaria alone accounting for as many as 1.5 million deaths annually. The long-term objective of the proposal research is to develop parasite- refractory mosquitoes that can be used in genetic control programs that will reduce the transmission of disease. This Competing Continuation describes our efforts to exploit molecular genetic methods for producing refractory strains of the Yellow Fever mosquito, Aedes aegypti. In laboratory-based experiments, we are developing techniques for producing hybrid genes that will express an antiparasite coding region under the control of an endogenous mosquito promoter. The SPECIFIC AIMS of this proposal are: 1) isolate and characterize cDNA and genomic clones for the genes encoding the salivary gland esterase (SG-EST) and anticoagulant; 2) characterize the promoters from the Apyrase (Apy), Maltase-like I (MalI), SG-EST and anticoagulant-encoding genes in homologous expression assays using dissected salivary glands and somatic infection with retroviruses; and 3) establish germline transformed strains of mosquitoes expressing a reporter gene under the control of the promoters of the salivary gland- specific genes, MalI and Apy,. Completion of these experiments will meet an objective of making the mosquito Ae. aegypti a vector organism that can be manipulated using transgenesis technologies. This will be an important milestone in the progress to use refractory mosquitoes to control the transmission of parasite diseases.